Osteoporosis is the disorder of too little bone. Although there are effective resorption inhibitors for osteoporosis (bisphosphonates, estrogen and calcitonin), these drugs do not cause substantial increases in bone mass. For patients with established osteoporosis, there is thus a need for anabolic therapeutic agents. We have developed a cell-based screening assay with which we can identify small molecular weight compounds which increase bone mass in rodent models of established osteoporosis. Our specific aims now are to 1) confirm the effects of a selected biologically active compound for its capacity to stimulate bone formation in vivo, 2) test the effects of this compound for its capacity to enhance bone formation following systemic administration in ovariectomized rats (an animal model of osteoporosis), and 3) test the effects of this selected compound administered systemically in a defect model of bone regeneration. Such compounds will be potential therapies not just for osteoporosis but also for other causes of bone loss such as segmental bone defects, periodontal disease and fracture repair. PROPOSED COMMERCIAL APPLICATION Osteoporosis is a major public health problem and a delayed fracture repair is a major cause of disability. Therapy is needed to increase the formation of bone and augment the bone that is lost. An ideal drug for these situations would be one that is orally available and could stimulate the formation of bone by increasing the endogenous production of bone growth factors. This project aims to characterize one such compound we have identified.